Alpha-fetoprotein

Aka: Alpha-fetoprotein, AFP, Maternal Serum AFP, MSAFP

1. Indications
   1. Pregnancy screening for congenital defect
      1. See Triple Screen
   2. Tumor Marker
      1. Cirrhosis with liver mass (Hepatocellular Carcinoma)
      2. Nonseminomatous germ cell tumor monitoring
         1. AFP used in combination with bHCG
2. Background
   1. Fetal glycoprotein with molecular weight of 70,000
   2. Sites of synthesis
      1. Embryonic Yolk Sac
      2. Developing gastrointestinal tract
      3. Liver
   3. AFP is major protein in developing fetus
      1. Decreases to undetectable level after birth
3. Interpretation
   1. Non-pregnant
      1. Normal AFP <5.4 ng/ml (5.4 ug/L)
      2. AFP >500 ng/ml unlikely to be from benign cause
      3. Nonseminomatous germ cell tumor
         1. Poor prognosis if AFP > 10,000 ng/ml at diagnosis
         2. AFP >10,000 associated with 50% five year survival
   2. Normal pregnancy
      1. See Triple Screen for interpretation
      2. Fetal serum AFP: Peaks at 3 mg/ml at 13 weeks
      3. Amniotic fluid AFP: Peaks at 30 ug/ml at 13 weeks
      4. Maternal Serum AFP: Peaks at 100 ng/ml at 30 weeks
4. Causes: Increased AFP in Non-pregnant States
   1. Benign causes of increased AFP
      1. Cirrhosis
      2. Acute or chronic active Viral Hepatitis
      3. Pregnancy (see below)
   2. Malignant causes of increased AFP
      1. Hepatocellular Carcinoma (usually AFP >1000 ng/ml)
      2. Testicular Cancer (non-seminomatous germ cell tumor)
      3. Gastric Cancer
      4. Biliary cancer
      5. Pancreatic Cancer
5. Causes: Abnormal Maternal Serum AFP (MSAFP) in Pregnancy
   1. Accurate Pregnancy Dating is critical
      1. AFP interpreted per gestational age
      2. Incorrect dates is most common cause for abnormal AFP
      3. AFP increases by gestational age in normal pregnancy
   2. Increased: Fetal malformation
      1. Neural Tube Defect
         1. Anencephaly
         2. Open spina bifida
      2. Sacrococcygeal teratoma
      3. Exomphalos
      4. Gastroschisis
      5. Cystic Hygroma
      6. Placental abnormalities
      7. Renal abnormalities
         1. Polycystic Kidney or absent Kidney
         2. Urinary obstruction
         3. Congenital Nephrosis
      8. Osteogenesis imperfecta
      9. Threatened Abortion or Fetal death in utero
      10. Decreased maternal weight or IUGR
      11. Multiple pregnancy (Twin Gestation)
   3. Decreased
      1. Incorrect gestational age (older than calculated)
      2. Trisomy 21 (Down Syndrome)
      3. Trisomy 18 (Edward's Syndrome)
      4. Hydatiform mole
      5. Fetal demise
      6. Increased maternal weight
6. Efficacy: Congenital defect detection in pregnancies
   1. Multiple of median (MOM) cut-off over 2.0 to 2.5
   2. False positive rate in normal pregnancies: 5%
   3. Trisomy 21 sensitivity: 21%
   4. Only marker in Triple Screen for Neural Tube Defect
      1. Anencephaly sensitivity: 90%
      2. Spina bifida sensitivity: 80%
7. Efficacy: Hepatocellular Carcinoma
   1. Increased in 80% of Hepatocellular Carcinoma cases
   2. Over 1000 ng/ml in 40% of Hepatocellular Carcinoma
8. Monitoring: Non-seminomatous germ cell tumor
   1. Initial: AFP with bHCG q1-2 months for 1 year
   2. Later: AFP with bHCG q3 months for 1 year
9. References
   1. Graves (2002) Am Fam Physician 65(5):915-22
   2. Johnson (2001) Clin Liver Dis 5:145-59